This K25 award will be used for successful transition for Dr. Mini Das, who is a physicist and optical engineer, to apply her skills to clinically relevant research in breast imaging. Her long-term goals are to be an independent researcher in this area and to develop a research program combining innovative physics with a thorough understanding of relevant biological processes, state of the art imaging techniques and real clinical needs for early stage breast cancer detection. In this proposal, Dr. Das will address some of the existing challenges in transitioning from 2D mammography to 3D breast images. Digital mammography (DM) has shown very high rate of detectability for microcalcifications (MCs), which are the primary precursor for invasive ductal carcinoma (DCIS). While digital breast tomosynthesis (DBT) is a modality waiting for FDA approval, it is not clear if it has been proven good enough to replace DM. Due to the differences in the attenuation properties and size/structure between MCs and masses, it is difficult to optimize DBT systems for best performance for both MC and mass detection from the same reconstructed image In light of these various challenges, the evaluation of the proposed variable dose DBT (VD-DBT) technique proposed here is of high significance. Here, a central projection slice equivalent to DM (primarily for MC detection) and a 3D reconstruction image (primarily for mass detection) can be acquired simultaneously. This method will also provide a smooth transition for the radiologists to obtain both a mammographic image and a 3D reconstructed image simultaneously with the lowest possible total dose. The second part of our proposal to investigate a penalised maximum likelihood (PML) reconstruction method with adjustable priors that can enable low noise image with improved SNR and edge preserving effects can improve the detection of masses using the 3D reconstructed image. This is also highly significant considering the need to reduce the total imaging dose in any proposed breast screening modality like DBT.